1. Field of the invention
The present invention relates to new 1-.beta.-methyl-2-thiolic carbapenem derivatives represented by the following general formula (I) ##STR2##
In the formula (I), R.sup.1 denotes hydrogen or anion; when R.sup.1 is hydrogen, R.sup.2 denotes 2-hydroxyethylamino, 3-hydroxypropylamino, 2-(R)-hydroxypropylamino, 2-(S)-hydroxypropylamino, 2-(R)-hydroxybutylamino, 2-(S)-hydroxybutylamino, 4-hydroxybutylamino, 1-hydroxymethylpropyl-(R)-amino, 1-hydroxymethylpropyl-(S)-amino, 5-hydroxypentylamino, 1-isopropyl-2-hydroxyethyl-(R)-amino, 1-isopropyl-2-hydroxyethyl-(S)-amino, 6-hydroxyhexylamino, 1-(1-methylpropyl)-2-hydroxyethyl-(S)-amino, 1-(2-methylpropyl)-2-hydroxyethyl-(R)-amino, 1-(2-methylpropyl)-2-hydroxyethyl-(S)-amino, 2-(1,3-dihydroxypropyl)amino, 2,3-dihydroxypropylamino, N-(4-hydroxypiperidino), N-(2-hydroxymethylpiperidino), N-(2-hydroxyethylpiperidino), N-(3,3-dimethylpiperidino), N-(3-methylpiperidino), N-(1,2,5,6-tetrahydropyridinyl), N-(2-hydroxymethylpyrrolidino), N-homopiperidino, N-thiazoyl, N-thiomorpholinyl or N-(3-hydroxymethylthiazolyl); and when R.sup.1 is anion, R.sup.2 denotes N-(S-alkylthiomorpholinylium) of following general formula (1 or N-(S-alkylthiazolium) cation of following general formula). ##STR3##
(In the above formula 1 and 2, R.sup.3 denotes methyl or low alkyl group of C.sub.2 -C.sub.4)
2. Description of the prior art
The well-known compound among the carbapenem antibiotics which is a subject compound of the present invention is an antibiotic thienamycine which is produced by incubating special Streptomyces species and is active against both gram-positive and gram-negative bacteria. (Reference to the U.S. Pat. No. 3,950,357, Kahan et.al.). But, there was a defect such that this compound was decomposed by an enzyme named Dehydropeptidase-1 (DHP-1), so that the effect of this compound was decreased.
To solve the above problem, the method in which a inhibitor of DHP-1 enzyme named cilastatine is used together with a thienamycine was suggested by MERCK and CO., Inc. (Reference to the European Patent No. 48,301), but there was a still problem for using this composite of cilastatine and thienamycine.